Fifty years of solvent denaturation.

The author has worked in the area of solvent denaturation and stabilization, off and on, for approximately 50 years. This paper is a personal view of the progress which has been made since 1950. The topic is limited to the development of thermodynamic molecular models for the interpretation of the unfolding and stabilization of protein structures. The story starts with the work in Kauzmann's laboratory shortly after World War II and proceeds through models for multisite binding, the linear denaturation curve, the special considerations required for understanding weak solvent exchange and a new model for the balance of solvent contact interactions and excluded volume.